Candidate: The applicant will begin as an Assistant Professor in the Division of Pediatric Otolaryngology at Cincinnati Children's Hospital Medical Center starting July 2003. Dr. Elluru has trained extensively, has a steadfast commitment to academic pediatric otolaryngology, and strives to excel as a physician and a scientist. To continue his training as a clinician-scientist he would like to pursue basic science research training in a mentored environment, with the goal of developing into an independent investigator. Environment: The research outlined in this application will be sponsored by Dr. Jeffrey A. Whitsett, Professor of Pediatrics and Director of the Division of Pulmonary Biology. Dr. Whitsett is a recognized leader in the field of lung physiology, developmental biology, and molecular genetics. Dr. Whitsett and Dr. Elluru have an outstanding and productive working relationship, which will be a tremendous asset in Dr. Elluru's development as a clinician-scientist. Cincinnati Children's Hospital and the Division of Pediatric Otolaryngology are strongly committed to supporting Dr. Elluru's training as a clinician-scientist and the development of a research program addressing congenital anomalies of the upper respiratory tract. The environment at the medical center is richly collegiate, and contains vast intellectual as well as material resources to nurture academic development. Research: Congenital anomalies of the upper respiratory tract, usually arising as a result of malformed cartilaginous support structures, result in significant childhood morbidity and mortality. Dr. Elluru will characterize the molecular mechanisms patterning the development of upper respiratory tract cartilage, with the long-term goal of 1) identifying the genetic and molecular basis of congenital upper respiratory tract lesions and 2) developing more efficacious treatment paradigms. The central hypothesis that will be tested in this grant application is that endodermal-mesodermal interactions, mediated by Sonic Hedgehog (SHH) and Fibroblast Growth Factor 18 (FGF-18), regulate the morphogenesis of cartilaginous support structures of the upper respiratory tract. The following specific aims will be accomplished: 1) Determine the role of Sox 9 in upper respiratory tract cartilage development, 2) Determine the role of FGF-18 in regulating the expression of Sox 9 and cartilage, and 3) Determine the role of SHH in regulating FGF-18, Sox 9 and cartilage expression. [unreadable] [unreadable]